In general, animal poisoning with organophosphorus insecticides is an all-or-none effect; once the acute phase of the poisoning is over, recovery is complete. In certain animals including man, however, exposure to some of these compounds results in delayed neurotoxicity. Recently, a new interest in this type of compounds has been developed since leptophos was implicated in the poisoning and paralysis of some workers in the Texas factory where it was produced and packaged. The overall objective of the total project is to determine the role of the skin as a potential portal of entry for these pesticides. This is determined by studying the ability of these compounds to cause delayed neurotoxicity following topical application, and by studying absorption, distribution, pharmacokinetics and metabolism of a topical single dose of 14C-labeled leptophos. The mechamism of delayed neurotoxicity will be investigated by studying the phosphorylation of mechanicokinetic proteins, and stability of lysosomal membranes, to determine if neuronal degeneration is initiated by the release of cellular hydrolases. In these studies, leptophos was proposed as the model compound, however, since this compound is now banned in the U.S. another neurotoxic insecticide, i.e., EPN will be included in some of the experiments.